CA2485339A1 - Radiopharmaceutical formulations - Google Patents
Radiopharmaceutical formulations Download PDFInfo
- Publication number
- CA2485339A1 CA2485339A1 CA002485339A CA2485339A CA2485339A1 CA 2485339 A1 CA2485339 A1 CA 2485339A1 CA 002485339 A CA002485339 A CA 002485339A CA 2485339 A CA2485339 A CA 2485339A CA 2485339 A1 CA2485339 A1 CA 2485339A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- radiopharmaceutical
- formula
- compound
- diluent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Radiopharmaceutical compounds are disclosed having a radionuclide chelating moiety and a targeting ligand, and optionally a linker. Formulations of compositions useful for making the radiopharmaceutical compounds contain a chelating ligand, a reducing agent, an exchange ligand and a stabilizer.</SD OAB>
Claims (37)
1. A radiopharmaceutical composition comprising:
a compound of Formula 1 a reducing agent;
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide, wherein R1 is H or is a linear or branched, saturated or unsaturated C1-4 alkyl chain that is optionally interrupted by one or two heteroatoms selected from N, O and S; and is optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R2 is a substituent defined by R1; or R1 and R2 may together form a S- to 8-membered saturated or unsaturated heterocyclic ring optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R3 is -H, -CH2OH, C2H4OH, or -t-butyl;
L is optional and is a linking group; and Z is a targeting molecule.
a compound of Formula 1 a reducing agent;
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide, wherein R1 is H or is a linear or branched, saturated or unsaturated C1-4 alkyl chain that is optionally interrupted by one or two heteroatoms selected from N, O and S; and is optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R2 is a substituent defined by R1; or R1 and R2 may together form a S- to 8-membered saturated or unsaturated heterocyclic ring optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R3 is -H, -CH2OH, C2H4OH, or -t-butyl;
L is optional and is a linking group; and Z is a targeting molecule.
2. A composition for the preparation of a radiopharmaceutical comprising:
a compound of Formula 1 a reducing agent;
an exchange ligand; and a stabilizer;
wherein R1 is H or is a linear or branched, saturated or unsaturated C1-4 alkyl chain that is optionally interrupted by one or two heteroatoms selected from N, O and S; and is optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R2 is a substituent defined by R1; or R1 and R2 may together form a 5- to 8-membered saturated or unsaturated heterocyclic ring optionally substituted by at least on group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R3 is -H, -CH2OH, C2H4OH, or -t-butyl;
L is optional and is a linking group; and Z is a targeting molecule.
a compound of Formula 1 a reducing agent;
an exchange ligand; and a stabilizer;
wherein R1 is H or is a linear or branched, saturated or unsaturated C1-4 alkyl chain that is optionally interrupted by one or two heteroatoms selected from N, O and S; and is optionally substituted by at least one group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R2 is a substituent defined by R1; or R1 and R2 may together form a 5- to 8-membered saturated or unsaturated heterocyclic ring optionally substituted by at least on group selected from halogen, hydroxyl, amino, carboxyl, C1-4 alkyl, aryl and C(O)Z;
R3 is -H, -CH2OH, C2H4OH, or -t-butyl;
L is optional and is a linking group; and Z is a targeting molecule.
3. A composition of claim 1 or 2 wherein R1 and R2 are methyl.
4. A composition of claim 1 or 2 wherein R3 is -CH2OH or C2H4OH.
5. A composition of claim 1 or 2 wherein R1 and R2 are methyl, and R3 is -CH2OH.
6. A radiopharmaceutical composition comprising a compound of Formula 1a a reducing agent;
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide, wherein L is optional and is a linking group; and Z is a targeting molecule.
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide, wherein L is optional and is a linking group; and Z is a targeting molecule.
7. A composition for the preparation of a radiopharmaceutical comprising a compound of Formula 1a a reducing agent;
an exchange ligand; and a stabilizer;
wherein L is optional and is a linking group; and Z is a targeting molecule.
an exchange ligand; and a stabilizer;
wherein L is optional and is a linking group; and Z is a targeting molecule.
8. A composition of claim 1, 2, 6 or 7 wherein Z is a bombesin analog.
9. A composition of claim 8 wherein Z is selected from the group consisting of SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID
NO:5; SEQ ID NO:6; and SEQ ID NO:7.
NO:5; SEQ ID NO:6; and SEQ ID NO:7.
10. A radiopharmaceutical composition comprising:
a compound of Formula 2 a reducing agent;
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide,.
a compound of Formula 2 a reducing agent;
an exchange ligand;
a stabilizer;
a diluent ; and a radionuclide,.
11. A composition for the preparation of a radiopharmaceutical comprising:
a compound of Formula 2 a reducing agent;
an exchange ligand; and a stabilizer.
a compound of Formula 2 a reducing agent;
an exchange ligand; and a stabilizer.
12. A composition of any one claims 1-11 wherein the reducing agent is selected from the group consisting of stannous salt, sodium borohydride, cupric salts, formamidine and sulfuric acid.
13. A composition of claim 12, wherein the reducing agent is stannous chloride.
14. A composition of any one of claims 1-13, wherein the exchange ligand is selected from the group consisting of gluconate, gentisic acid and glucoheptonate.
15. A composition of claim 14 wherein the exchange ligand is gluconate.
16. A composition of any one of claims 1-15 wherein the stabilizer is selected from the group consisting of gentisic acid, maltose and ascorbic acid.
17. A composition of claim 16, wherein the stabilizer is gentisic acid.
18. A composition of any one of claims 1-17, further comprising a solubilizer.
19. A composition of claim 18, wherein the solubilizer is a cyclodextrin.
20. A composition of claim 19, wherein the solubilizer is hydroxypropyl-.gamma.-cyclodextrin.
21. A composition of any one of claims 1, 3-6, 8-10, 12-20 wherein the diluent is selected from the group consisting of ethanol, water and saline.
22. A composition of claim 21, wherein the diluent is ethanol.
23. A radiopharmaceutical composition comprising:
a compound of Formula 2 Formula 2;
stannous chloride;
gluconic acid;
gentisic acid;
ethanol; and a radionuclide.
a compound of Formula 2 Formula 2;
stannous chloride;
gluconic acid;
gentisic acid;
ethanol; and a radionuclide.
24. A composition for the preparation of a radiopharmaceutical comprising:
a compound of Formula 2 stannous chloride;
gluconic acid; and gentisic acid.
a compound of Formula 2 stannous chloride;
gluconic acid; and gentisic acid.
25. A composition of claim 23 or 24, further comprising hydroxypropyl-.gamma.-cyclodextrin.
26. A radiopharmaceutical composition of any one of claims 1, 3-6, 8-10, 12-22, wherein the compound of Formula 1 is present at less than 10 µg per mL of diluent.
27. A radiopharmaceutical composition of any one of claims 1, 3-6, 8-10, 12-22, wherein the compound of Formula 1 is present at less than 5 µg per mL of diluent.
28. A radiopharmaceutical composition of any one of claims 1, 3-6, 8-10, 12-22, wherein the radiopharmaceutical can be prepared and administered to a subject without purification.
29. A radiopharmaceutical composition of any one of claims 1, 3-6, 8-10, 12-22, wherein the RCP of the composition is greater than or equal to about 90% at about 15 minutes.
30. A composition of any one of claims 2-5, 7-9, 11-20, wherein the compound of Formula 1 is present in an amount,such that the resulting radiopharmaceutical contains less than 10 µg per mL of a diluent.
31. A composition of any one of claims 2-5, 7-9, or 11-20, wherein the compound of Formula 1 is present in an amount such that the resulting radiopharmaceutical contains less than 5 mu.g per mL of diluent.
32. A composition of any one of claims 2-5, 7-9, or 11-20, wherein the resulting radiopharmaceutical can be prepared and administered to a subject without purification.
33. A composition of any one of claims 2-5, 7-9, or 11-20, wherein the RCP of the resulting radiopharmaceutical is greater than or equal to about 90% at about 15 minutes.
34. A composition of any one of claims 1-32, further comprising a detergent.
35. A composition of any one of claims 2-5, 7-9, 11-20 or 29-33, further comprising a detergent, wherein the composition is in lyophilized form.
36. A composition of any one of claims 2-5, 7-9, 11-20 or 29-33, further comprising a diluent, optionally contained in a separate container.
37. A composition of claim 34, wherein the detergent is cyclohexyl-n-methyl-.beta.-D-maltoside or n-Hexyl-.beta.-D-glucopyranoside.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37745402P | 2002-05-03 | 2002-05-03 | |
| US60/377,454 | 2002-05-03 | ||
| PCT/US2003/013936 WO2003092743A1 (en) | 2002-05-03 | 2003-05-05 | Radiopharmaceutical formulations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2485339A1 true CA2485339A1 (en) | 2003-11-13 |
| CA2485339C CA2485339C (en) | 2012-02-14 |
Family
ID=29401500
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2485339A Expired - Fee Related CA2485339C (en) | 2002-05-03 | 2003-05-05 | Radiopharmaceutical formulations |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7556795B2 (en) |
| EP (1) | EP1503804A4 (en) |
| JP (1) | JP4885448B2 (en) |
| CN (1) | CN100471523C (en) |
| AU (1) | AU2003239351B2 (en) |
| CA (1) | CA2485339C (en) |
| WO (1) | WO2003092743A1 (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7611692B2 (en) | 2003-01-13 | 2009-11-03 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| US7850947B2 (en) | 2003-01-13 | 2010-12-14 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| US7226577B2 (en) | 2003-01-13 | 2007-06-05 | Bracco Imaging, S. P. A. | Gastrin releasing peptide compounds |
| US8420050B2 (en) | 2003-01-13 | 2013-04-16 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| US7922998B2 (en) * | 2003-01-13 | 2011-04-12 | Bracco Imaging S.P.A. | Gastrin releasing peptide compounds |
| CA2783275A1 (en) * | 2003-07-24 | 2005-02-03 | Bracco Imaging S.P.A. | Stable radiopharmaceutical compositions and methods for their preparation |
| WO2007109475A2 (en) * | 2006-03-16 | 2007-09-27 | Bracco Imaging S.P.A. | Chelation of metals to thiol groups using in situ reduction of disulfide-containing compounds by phosphines |
| WO2008009444A1 (en) * | 2006-07-19 | 2008-01-24 | Van Dulmen, Adrianus, A. | Use of ethanol for stabilizing a single-vial liquid formulation of a radiolabeled peptide |
| US20080213181A1 (en) * | 2006-12-21 | 2008-09-04 | Bristol-Myers Squibb Pharma Company | Preparation of Paramagnetic Nanoparticles Conjugated to Leukotriene B4 (LTB4) Receptor Antagonists, and Their Use as MRI Contrast Agents for the Detection of Infection and Inflammation |
| US8436140B2 (en) * | 2008-06-02 | 2013-05-07 | Washington University | Natriuretic peptide-mediated imaging of atherosclerotic plaque |
| CN103467504B (en) * | 2013-09-23 | 2015-06-24 | 武汉工程大学 | 18F-fluorine-labeled porphyrin-isozaindene free radical complex and its synthesis method |
| CN103435684B (en) * | 2013-09-23 | 2015-10-28 | 武汉工程大学 | 18f-fluorine mark pentapeptide title complex and synthetic method |
| GB201402132D0 (en) * | 2014-02-07 | 2014-03-26 | South African Nuclear Energy | A method of producing ethylenedicysteine deoxyglucosamine (ECDG) or a salt thereof and its application in a kit |
| AU2019251769A1 (en) | 2018-04-11 | 2020-10-15 | Clarity Pharmaceuticals Limited | Formulations and kits for radiotherapy and diagnostic imaging |
| GB201915206D0 (en) * | 2019-10-21 | 2019-12-04 | Ge Healthcare Ltd | Use of cyclodextrins as a radiostabilizer |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4364920A (en) * | 1975-04-30 | 1982-12-21 | Medi-Physics, Inc. | Stable diagnostic reagents |
| US4233284A (en) * | 1978-03-31 | 1980-11-11 | The Procter & Gamble Company | Stabilized radiographic scanning agents |
| DE78642T1 (en) * | 1981-10-30 | 1983-10-27 | Amersham International Plc, Amersham, Buckinghamshire | RADIOPHARMACEUTICAL PREPARATION BASED ON TECHNETIUM-99M AND REAGENT FOR THE PRODUCTION THEREOF. |
| US5753206A (en) * | 1995-06-07 | 1998-05-19 | Immunomedics, Inc. | Radiometal-binding analogues of luteinizing hormone releasing hormone |
| EP0881489A1 (en) * | 1995-12-29 | 1998-12-02 | Wako Pure Chemical Industries Ltd | Method for determining viable cell count |
| EP1005479A4 (en) * | 1997-04-10 | 2002-12-18 | Life Technologies Inc | Rna isolation reagent and methods |
| US6200546B1 (en) | 1997-04-22 | 2001-03-13 | The Curators Of The University Of Missouri | Gastrin receptor-avid peptide conjugates |
| US7060247B2 (en) * | 1997-04-22 | 2006-06-13 | The Curators Of The University Of Missouri | Gastrin receptor-avid peptide conjugates |
| US6056941A (en) * | 1999-07-28 | 2000-05-02 | Bracco Research Usa | Kit for the preparation of technetium TC 99m teboroxime myocardial perfusion agent |
| US6685914B1 (en) * | 1999-09-13 | 2004-02-03 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants for metallopharmaceuticals |
-
2003
- 2003-05-05 JP JP2004500926A patent/JP4885448B2/en not_active Expired - Fee Related
- 2003-05-05 WO PCT/US2003/013936 patent/WO2003092743A1/en active Application Filing
- 2003-05-05 AU AU2003239351A patent/AU2003239351B2/en not_active Ceased
- 2003-05-05 EP EP03733935A patent/EP1503804A4/en not_active Withdrawn
- 2003-05-05 US US10/513,586 patent/US7556795B2/en not_active Expired - Fee Related
- 2003-05-05 CA CA2485339A patent/CA2485339C/en not_active Expired - Fee Related
- 2003-05-05 CN CNB03812954XA patent/CN100471523C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4885448B2 (en) | 2012-02-29 |
| AU2003239351B2 (en) | 2008-03-13 |
| AU2003239351A1 (en) | 2003-11-17 |
| WO2003092743A1 (en) | 2003-11-13 |
| CN100471523C (en) | 2009-03-25 |
| US20060034760A1 (en) | 2006-02-16 |
| WO2003092743A9 (en) | 2004-04-01 |
| JP2005526116A (en) | 2005-09-02 |
| US7556795B2 (en) | 2009-07-07 |
| CN1658907A (en) | 2005-08-24 |
| EP1503804A4 (en) | 2009-03-18 |
| EP1503804A1 (en) | 2005-02-09 |
| CA2485339C (en) | 2012-02-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20140506 |